There are a number of occasions and sites where it would be beneficial to modify linear biological macromolecules, such as in disease states and during surgery. Examples where linear macromolecules are problematic are acute and chronic otitis media and sinusitis, acute and chronic inflammatory disorders of the respiratory tract (including cystic fibrosis), disorders of the alimentary and genito-urinary tracts, and during surgical procedures on ducts and surfaces of body cavities filled or covered by thickened secretions or exudates. There are no biologically efficacious substances or methods typically used for alteration or removal of these species of macromolecules, which in pathological situations can result in acute and chronic morbidity and mortality.
On the simple basis of observed viscosity or lubricity, older physiology texts classified secretions into thick or thin. Thick secretions were described as “mucoid”, whereas thin secretions were considered “serous” in nature. These ill-defined archaic terms are still in use and have not been accurately defined and categorized. The term “serous” is applied to the sparse, thin secretions encountered universally in the large body cavities, pleura, pericardium, peritoneum, joints and tendon sheaths. This thin secretion is termed “serous” in that, like serum, it does not clot. In the last decade however, serous fluid in body cavities, was for the first time accurately defined as a secretion of mesothelium in which phospholipid microbodies were the predominant element in conferring high lubricity and non-stick properties (Dobbie J W, (1988) Ultrastructural similarities between mesothelium and Type II pneumocytes and their relevance to phospholipid surfactant production by the peritoneum In: Khanna R, Nolph K D, Prowant B, Eds: Advances in Continuous Ambulatory Peritoneal Dialysis. University of Toronto Press, Toronto, pp 32-41; Dobbie J W, Pavlina T, Lloyd J, Johnson R C. (1988); Am J Kid Dis., 12:31-36; Dobbie J W, Lloyd J K. (1989), Petit Dial Int, 9:215-221). Subsequently it has been shown that not only mesothelium but many other tissues in respiratory, alimentary and reproductive tracts contain varying densities of “serous” cells, which secrete a similar substance.
Invisible to light and electron microscopy for so long, these findings have recently been responsible for the concept that the secretory system for these phospholipid microbodies constitutes a hitherto unrecognized major biological system throughout the animal kingdom (Dobbie J W. (1996) Perit Dial Int. 16:574-581).
Widespread throughout the animal kingdom, the secretion of mucus from body surfaces, in association with underlying motile projections of cell surfaces, cilia, together constitutes an important mechanical system for automatic clearance of potentially noxious substances. In lung, the mucociliary clearance system is the first line of defense against inhaled particulates, aerosols and pathogens, into its airways. Such materials are adsorbed out of the air stream onto the mucous gel contained within the airway surface liquid, which coats the ciliated epithelium. Despite the focus of intensive research in recent years, particularly in relation to the pathogenesis of cystic fibrosis, there remain unsolved biophysical problems in understanding the function of mucociliary clearance in all body surfaces. It is with respect to the identification of compositions for the treatment of diseases and conditions characterized by the preponderance of thick mucous secretions that the present application is directed.